title: Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats.
abstract: This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.
authors.affiliation: Department of Anesthesiology and Postoperative Intensive Care Medicine, University of Cologne, Kerpener Str. 62, D-50937 Cologne, Germany. peter.teschendorf@uk-koeln.de
authors.forename: Peter
authors.initials: P
authors.lastname: Teschendorf
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Padosch
authors.forename: Fabian
authors.initials: F
authors.lastname: Spöhr
authors.forename: Markus
authors.initials: M
authors.lastname: Albertsmeier
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Yeong-Hoon
authors.initials: YH
authors.lastname: Choi
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Böttiger
authors.forename: Erik
authors.initials: E
authors.lastname: Popp
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation; D006323:Heart Arrest / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis
chemical_list: C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases